Topical Insulin for Ocular Surface Interface in Dry Eye Disease

Patients fulfilling the selection criteria will be enrolled from eye OPD of KTH. A written informed consent will be taken after explaining the purpose of study. Data will be collected on a pre-designed structured proforma. Demographic data including age, gender, educational status, socioeconomic status will be noted. Each participant will undergo a complete history assessment and the OSDI score will be calculated after taking extensive history. Ophthalmologic examination, including visual acuity, refraction, slit-lamp examination, corneal staining, schirmer test and TBUT will be performed in each patient. Both eyes will be selected for each secondary outcome measure (TBUT \& SCHIRMER TEST). However, only one OSDI score could only be obtained per patient for assessing primary outcome. All the previous medications used for dry eye will be stopped Participants' eyes will be randomized by blocked randomization in a 1:1 ratio to be treated with topical artificial tears (group I) and topical insulin 1U/ml (group II). The patients will be masked for the treatment, but not the principle investigator. Another investigator will prepare the topical insulin according to a written protocol. Participants will be given a white, unlabeled eye dropper containing the same volume of artificial tears or topical insulin for groups I and II respectively. Group I will receive artificial tears (control group) four times daily. Group II will receive topical insulin of 1u/ml four times daily. Follow-up assessments will be conducted at 4, 8 and 12 weeks for each participant to measure changes in TBUT, schirmer test, and OSDI score.

• Artificial tear (Drug), also known as ARTIFICIAL TEARS: commercially available artificial tears will be used consisting of same ingredients.
• insulin human (Drug), also known as INSULIN: injection humulin will be used to make topical insulin drops

Primary outcomes

• OSDI Score [Baseline to Week 12]: The Ocular Surface Disease Index (OSDI) is a 12-item patient-reported questionnaire assessing dry eye symptom severity and its impact on vision-related function. The OSDI score ranges from 0 to 100, with higher scores indicating worse outcomes (greater symptom severity). This outcome reports the continuous OSDI score at baseline, week 4, week 8 and at Week 12 following initiation of treatment. A reduction in OSDI score from baseline indicates improvement in dry eye symptoms. An OSDI score of <20 at Week 12 was considered the predefined threshold for clinically meaningful symptomatic improvement. .

Secondary outcomes

• SCHIRMER TEST [Baseline to Week 12]: Schirmer's test (without anaesthesia) measures aqueous tear production as the length of wetting on a standardized 35 mm filter paper strip over 5 minutes, range 0-35 mm. Higher values indicate better outcome (greater tear production)." Unit of Measure: "mm.The treatment will be deemed effective if Schirmer's test values are above 10mm after 5 minutes, TBUT of more than 10 seconds s achieved at 12 weeks of the initiation of treatment.
• Tear Film Break up Time [Baseline to Week 12]: Fluorescein tear break-up time (TBUT) measures tear film stability as the time, in seconds, for the first dry spot to appear in the stained tear film after a blink, mean of three readings. Higher values indicate better outcome (more stable tear film). Unit of Measure: seconds Change in Tear Break-Up Time (TBUT) at 12 Weeks

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients having Schirmer's test values of less than 10mm after 5 minutes of the procedure recording plus a non-invasive tear breakup time (TBUT) of less than 10 seconds and the Ocular Surface Disease Index (OSDI) of more than 32 (diagnosed as dry eye disease as per the operational definition of this study).
* any gender.
* aged 18 years and above.

Exclusion Criteria:

* Patients with active ocular infection, severe ocular surface disease other than Dry eye disease, and those who have undergone ocular surgery within the past 6 months.
* Under 18 years old

Participant flow

Outcome results

• OSDI Score (Primary), Mean, score on a scale: Topical Insulin Group/Arm 44.67 +/- 16.70; Artificial Tears Group/Arm 47.81 +/- 15.85 (p 0.032)
• SCHIRMER TEST (Secondary), Mean, mm: Topical Insulin Group/Arm 6.36 +/- 1.30; Artificial Tears Group/Arm 6.11 +/- 1.17 (p <0.001)
• Tear Film Break up Time (Secondary), Mean, seconds: Topical Insulin Group/Arm 6.48 +/- 1.70; Artificial Tears Group/Arm 6.47 +/- 1.49 (p <0.001)

Adverse events

Time frame: 12 week time

Limitations and caveats: Single-center study. Follow-up time limited to 12 weeks (short follow-up) inflammatory markers were not analysed. subgroup analyses were post-hoc and exploratory which requires cautious interpretation

• Kawahara A. Treatment of Dry Eye Disease (DED) in Asia: Strategies for Short Tear Film Breakup Time-Type DED. Pharmaceutics. 2023 Nov 5;15(11):2591. doi: 10.3390/pharmaceutics15112591. PMID 38004570
• Zhang X, Zhao L, Deng S, Sun X, Wang N. Dry Eye Syndrome in Patients with Diabetes Mellitus: Prevalence, Etiology, and Clinical Characteristics. J Ophthalmol. 2016;2016:8201053. doi: 10.1155/2016/8201053. Epub 2016 Apr 26. PMID 27213053
• Aniah Azmi N, Bastion MC. Short-Term Results of Trial of Topical Insulin for Treatment of Dry Eyes in Diabetics. Eye Contact Lens. 2020 Jan;46 Suppl 1:S25-S32. doi: 10.1097/ICL.0000000000000623. PMID 31145207
• Tahmaz V, Menghesha L, Stern ME, Holtick U, Scheid C, Steven P. Insulin eye drops for severe refractory chronic ocular graft-versus-host disease. Bone Marrow Transplant. 2024 Jul;59(7):1031-1033. doi: 10.1038/s41409-024-02272-9. Epub 2024 Apr 10. No abstract available. PMID 38600163
• Results publication: Markoulli M, Hui A. Emerging targets of inflammation and tear secretion in dry eye disease. Drug Discov Today. 2019 Aug;24(8):1427-1432. doi: 10.1016/j.drudis.2019.02.006. Epub 2019 Feb 22. PMID 30802601

• Study Protocol and Statistical Analysis Plan (PDF, 2026-06-13)

• Shafiq Tanvee, MBBS, FCPS, Principal investigator, KHYBER TEACHING HOSPITAL PESHAWAR KPK PAKISTAN